Shikonin inhibits inflammatory cytokine production

Shikonin, which is derived from Lithospermum erythrorhizon, a herb used in traditional medicine, has long been considered to be a useful treatment for various diseases in traditional oriental medicine. Shikonin has recently been reported to have several pharmacological properties, e.g., it has anti-microbial, anti-tumor, and anti-inflammatory effects. The aim of this study was to examine whether shikonin is able to influence the production of interleukin (IL)-6, IL-8, and/or chemokine C-C motif ligand (CCL)20, which contribute to the pathogenesis of periodontal disease, in human periodontal ligament cells (HPDLC). The production levels of IL-6, IL-8, and CCL20 in HPDLC were determined using an ELISA. Western blot analysis was used to detect nuclear factor kappa B (NF-κB) pathway activation in HPDLC. Shikonin prevented IL-1β- or tumor necrosis factor (TNF)-α-mediated IL-6, IL-8, and CCL20 production in HPDLC. Moreover, we found that shikonin suppressed the phosphorylation and degradation of inhibitor of kappa B-alpha (IκB-α) in IL-1β- or TNF-α-stimulated HPDLC. These findings suggest that shikonin could have direct beneficial effects against periodontal disease by reducing IL-6, IL-8, and CCL20 production in periodontal lesions

genipinはTNF-αが誘導するヒト歯根膜細胞のMMP-1およびMMP-3産生を抑制する

Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of inflammatory diseases in traditional oriental medicine. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify matrix metalloproteinase (MMP)-1 and MMP-3, which are related to the destruction of periodontal tissues in periodontal lesion, expression in tumor necrosis factor (TNF)-a-stimulated human periodontal ligament cells (HPDLCs). Genipin prevented TNF-a- mediated MMP-1 and MMP-3 productions in HPDLCs. Moreover, genipin could suppress not only extracellular signal-regulated kinase (ERK) and Jun-N-terminal kinase (JNK) phosphorylations but also AMP-activated protein kinase (AMPK) phosphorylation in TNF-a-stimulated HPDLCs. Inhibitors of ERK and AMPK could inhibit both MMP-1 and MMP-3 productions. Moreover, we revealed the ERK inhibitor suppressed AMPK phosphorylation in TNF-a-stimulated HPDLCs. These data provide a new mechanism through which genipin could be used for the treatment of periodontal disease to prevent MMPs expression in periodontal lesion

Melatonin inhibits CXCL10 and MMP-1 production

Melatonin is a hormone that is mainly secreted by the pineal gland and exhibits a wide spectrum of activities, including antioxidant functions. Melatonin has been detected in gingival crevicular fluid. However, the role of melatonin in periodontal tissue is still uncertain. The aim of this study was to examine the effects of melatonin on inflammatory mediator expression in human periodontal ligament cells (HPDLC). Interleukin (IL)-1β induced CXC chemokine ligand (CXCL)10, matrix metalloproteinase (MMP)-1, and tissue inhibitors of metalloproteinase (TIMP)-1 production in HPDLC. Melatonin decreased CXCL10 and MMP-1 production and increased TIMP-1 production in IL-1β-stimulated HPDLC. Western blot analysis showed that melatonin inhibited p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) phosphorylation, and IκB-α degradation and phosphorylation in IL-1β-stimulated HPDLC. These results suggest that melatonin might inhibit Th1 cell migration by reducing CXCL10 production. Moreover, melatonin might inhibit soft tissue destruction by decreasing MMP-1 production in periodontal lesions

IL-4 Modulates Chemokine Productions in Fibroblast

Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs). Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt) and signal transducer and activator of transcription (STAT)6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions

Gomisin N inhibits inflammatory cytokine production.

Gomisin N, which is a lignan isolated from Schisandra chinensis, has some pharmacological effects. However, the anti-inflammatory effects of gomisin N on periodontal disease are uncertain. The aim of this study was to examine the effect of gomisin N on inflammatory mediator production in tumor necrosis factor (TNF)-α-stimulated human periodontal ligament cells (HPDLC). Gomisin N inhibited interleukin (IL)-6, IL-8, CC chemokine ligand (CCL) 2, and CCL20 production in TNF-α-stimulated HPDLC in a dose-dependent manner. Moreover, we revealed that gomisin N could suppress extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) phosphorylation in TNF-α-stimulated HPDLC though protein kinase B (Akt) phosphorylation was not suppressed by gomisin N treatment. In summary, gomisin N might exert antiinflammatory effects by attenuating cytokine production in periodontal ligament cells via inhibiting the TNF-α-stimulated ERK and JNK pathways activation

IL-29 enhances CXCL10 production

Interleukin-29 (IL-29) is a cytokine belonging to the type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay. We used Western blot analysis to detect IL-29 receptor expression and the phosphorylation levels of signal transduction molecules, including p38 mitogen-activated protein kinases (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor (NF)-κB p65, in the TR146 cells. The TR146 cells expressed the IL-29 receptor. IL-29 induced CXCL10 production in the TR146 cells. IL-29 significantly enhanced CXCL10 production in tumor necrosis factor (TNF)-α-stimulated TR146 cells. The p38 MAPK, STAT3, and NF-κB pathways were found to be related to the IL-29-induced enhancement of CXCL10 production in TNF-α-stimulated TR146 cells. IL-29 promotes T helper 1 cell accumulation in periodontal lesions by inducing CXCL10 production in oral epithelial cells

Alkannin inhibits CCL3 and CCL5 production

Alkannin, which is found in Alkanna tinctoria, a member of the borage family, is used as a food coloring. Alkannin has recently been reported to have certain biological functions, such as anti-microbial and anti-oxidant effects. It is known that CC chemokine receptor (CCR) 5-positive leukocytes contribute to alveolar bone resorption in periodontal lesions. The aim of this study was to examine whether alkannin inhibits the production of CC chemokine ligand (CCL) 3 and CCL5, which are CCR5 ligands, in human periodontal ligament cells (HPDLC). Interleukin (IL)-1β induced CCL3 and CCL5 production in HPDLC. Alkannin inhibited IL-1β-mediated CCL3 and CCL5 production in HPDLC in a dose-dependent manner. Moreover, we revealed that alkannin suppressed inhibitor of kappa B-α degradation in IL-1β-stimulated HPDLC. In addition, a nuclear factor (NF)-κB inhibitor significantly inhibited CCL3 and CCL5 production in IL-1β-stimulated HPDLC. These results demonstrate that alkannin inhibits CCR5 ligand production in IL-1β-stimulated HPDLC by attenuating the NF-κB signaling pathway

Individual Radiation Exposure Dose Due to Support Activities at Safe Shelters in Fukushima Prefecture

Immediately after the accidents in the nuclear power stations in Fukushima on March 11, the Japanese Government ordered the evacuation of the residents within a 20-km radius from the station on March 12, and asked various institutions to monitor the contamination levels of the residents. Hirosaki University, which is located 355 km north of Fukushima City, decided to send support staff to Fukushima. This report summarizes the results of the exposure of 13 individual teams from March 15 to June 20. The support teams surveyed more than 5,000 people during this period. Almost all subjects had external contamination levels of less than 13 kcpm on Geiger-Müller (GM) survey meter, which is categorized as “no contamination level.” The 1st team showed the highest external exposure dose, but the 4th team onward showed no significant change. Subsequently, the internal radiation exposure was measured using a whole body counter that indicated undetectable levels in all staff members. Although the measured external radiation exposure dose cannot have serious biological effects on the health of an individual, a follow-up study of the residents in Fukushima and other regions where the radioactive material has spread will be required for a long time

Spatiotemporal Control of Ice Crystallization in Supercooled Water via an Ultrashort Laser Impulse

Takahashi H., Kono T., Sawada K., et al. Spatiotemporal Control of Ice Crystallization in Supercooled Water via an Ultrashort Laser Impulse. Journal of Physical Chemistry Letters, 14(19), 4394-4402, 18 May 2023: © 2023 American Chemical Society. DOI: 10.1021/acs.jpclett.3c00414.Focused irradiation with ultrashort laser pulses realized the fine spatiotemporal control of ice crystallization in supercooled water. An effective multiphoton excitation at the laser focus generated shockwaves and bubbles, which acted as an impulse for inducing ice crystal nucleation. The impulse that was localized close to the laser focus and accompanied by a small temperature elevation allowed the precise position control of ice crystallization and its observation with spatiotemporal resolution of micrometers and microseconds using a microscope. To verify the versatility of this laser method, we also applied it using various aqueous systems (e.g., plant extracts). The systematic study of crystallization probability revealed that laser-induced cavitation bubbles play a crucial role in inducing ice crystal nucleation. This method can be used as a tool for studying ice crystallization dynamics in various natural and biological phenomena

Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16–40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan